Development of new preventatives and therapies for AIDS requires in vivo models for infection. Rabbits are the only non-primate species reported to acquire systemic HIV-1 infection. Although the utility of this model is limited by low efficiency of infection, it was determined that the biology of HIV-1 transmission is closely modeled in rabbits. The rabbit was used here to study perinatal HIV-1 infection, specifically to investigate the possibility that infected cells originating in the mother mediate HIV-1 transmission. HIV-1-infected human T cells were administered to pregnant rabbits and offspring, newborn to 1.5 years of age were evaluated. HIV-1 was detected in 11 of 19 vaginally delivered offspring born to mothers given infected cells during gestation. Interstitial pneumonias or lymphoid organ lesions similar to those seen in human pediatric AIDS, occurred in some. Persistence of inoculum cell (HLA)-specific gene sequences in offspring indicated that vertical transmission can be effected by T cell-associated virus. Other investigations concern the use of the rabbit as a general model for HIV-1 infection. Recent reports showing that chemokine receptors facilitate cellular entry by HIV provide opportunities to develop transgenic animals which allow facilitated virus attachment and entry. Rabbits exhibit no apparent limitation to post-entry molecular replication of HIV, as is the case with other small animal model systems. Preliminary in vitro data indicate that increased levels of virus production occur from transgenic rabbit lymphocytes expressing human CD4 (HuCD4), a major cell surface receptor for HIV gp 120 envelope protein, when compared to native rabbit lymphocytes infected with HIV-1. In addition, virus infection resulted in apoptosis of CD4+ and CD4- lymphocytes from human CD4 transgenic rabbits. Current studies performed in collaboration, suggest that HIV replication in the rabbit cell lines transfected with both human CD4 and chemokine receptors approaches that in human cell lines.